The major objective of this research is to further characterize the behavioral effects of chronic psychostimulants with particular emphasis on amphetamine and to elucidate the mechanism underlying these effects. These studies will include an examination of: (1) the persistence of the enhanced responsiveness (which is apparent after discontinuation of amphetamine administration) with respect to dose chronicity and behavioral components; (2) long-term behavioral effects of other drugs such as cocaine, morphine, and caffeine which at various doses acutely produce amphetamine-like behavioral responses; (3) the amphetamine-induced behavioral augmentation following manipulation of monoamine pathways with selective electrolytic lesions and specific neurotoxins; (4) pharmacokinetics of amphetamine (using GCMS procedures) with respect to brain regional, metabolic, and temporal patterns; (5) central infusion of indirect and direct acting agents (e.g., dopamine, norepinephrine and apomorphine) to determine the relative contribution of the various monoamine systems and possible alterations of pre- and postsynaptic mechanisms following multiple amphetamine administration. In related studies the role of catecholamines and serotonin will be evaluated with respect to their relative roles in the elaboration of the response to amphetamine and related psychomotor stimulants, electrolytic lesions, neurotoxins (6-hydroxydopamine, 5,7-dihydroxytryptamine) and systemic administration of drugs such as clonidine will be employed to selectively manipulate specific monoamine pathways. Electrophysiological correlates, in the form of single unit extracellular recording, will be conducted in conjunction with many of these studies. The research involving the behavioral characterization of the morphinomimetic endogenous brain peptides will also be extended. Studies are currently directed at: (1) regional betaendorphin administration to identify brain sites which subserve the various components of the behavioral effects of beta-endorphin, and (2) pharmacological interactions, in order to elucidate the neurochemical mechanisms involved.